Synthesis of di-aryl cyclic ethers



Patented Sept. 4, 1951 SYNTHESIS OF DI-ARYL CYCLIC ETHERS Milton Orchin and Elkin Oscar Woolfolk, Pittsburgh, Pa., assignors to the United States of America as represented by the Secretary of the Interior No Drawing. Application February 28, 1949, Serial No. 78,884

(Granted under the act of March 3, 1883, as amended April 30, 1928; 370 0. G. 757) Claims.

The invention herein described and claimed may be manufactured and used by or for the Government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor.

This invention relates to aromatic cyclic ethers and methods of preparing them.

It has previously been shown by one of the present inventors and Reggel (Am. Chem. Soc. 68, 505 (1947)) that l-phenylnaphthalene undergoes cyclodehydrogenation to fluoranthene and that there is only slight migration of the phenyl group to give 2-phenylnaphthalene. In this reaction, there is intramolecular loss of hydrogen between the benzene nucleus and the naphthalene nucleus. Or more generically, it may be considered dehydrogenation between two aromatic nuclei.

We have found that cyclic ethers of the general formula wherein R is a radical from the class consisting of phenyl, naphthyl, and hydrogenated naphthyl groups, and R is the same or a different radical from the same class, may be prepared from two directly coupled aryl radicals, one of which has a hydroxyl group or low molecular weight alkoxy group in the ortho position to the carbon atom in the ring which is directly joined to the other aromatic radical. The reactant may be represented as where X represents H, CH3, or C2H5, etc. When H is hydrogen, this illustrated reactant will be Zhydroxy-l-phenyl naphthalene. The cyclic ether from this specific di-aryl phenol is 1,9- benzoxanthene Other di-aryl phenolic compounds in which the hydroxy group is so situated that loss of a hydrogen molecule between the hydroxyl group and another aromatic ring will form a fiveor sixmembered ring, are suitable for cyclization by this present method. Such compounds are 1- hydroxy-B-phenylnaphthalene and e-phenanthrol. Important derivatives of the latter compound are amenable to this reaction.

Some of the cyclic ethers of the types prepared by our process are a class suitable for use as biological products. Consequently, they are either distinctly valuable or potentially so.

It is an object of the present invention to convert directly-joined di-aryl compounds in which one of these aryl radicals contains an ortho substituted group, OH, CH3, or C2H5, into a di-aryl cyclic ether. The aryl groups may be similar or dissimilar. The reaction may be carried out in the liquid phase. It is a more particular object of this present invention to achieve this synthesis under vapor-phase conditions.

It has been mentioned supra that the reactant compound may have a methoxy or ethoxy radical group in the ortho position instead of a phenolic hydroxyl group. These alkoxy groups are easily converted to the phenol group. This may be as a separate step or simultaneous with the step of cyclodehydrogenation.

Various catalysts may be used to cause cyclodehydrogenation of the above type phenols. In

the liquid phase, we prefer to use a type of palladium-charcoal c-ataylst. For the vapor phase method, we prefer to employ chromiaalumina; the temperature of the reaction is higher.

Having explained the nature of our invention, a fuller understanding of it may be gained from a description of several specific embodiments. The.

following examples will further illustrate howour invention may be carried out in practice, but the invention is not restricted to these examples.

Example I anisyl-magnesium bromide. This reaction may be represented by the equation;

MgBr

CH3 O CH3 Mg(ethe1') To this solution of the Grignard reagent, there was added dropwise with stirring a solution of 64.0 grams of pure vacuum fractionated l-tetralone (II) in 150 cc. of dry ethyl ether. After all the tetralone had been added, the mixture was refluxed for 17 hours. ethyl ether was replaced by an equivalent volume of benzene. The mixture was poured into ice and ammonium chloride solution, The organic layer was separated, washed well with water and saturated sodium chloride solution, and filtered through sodium sulfate. After removal of most of the solvent in vacuo, beautiful colorless crystals separated. These weighed 30.58 grams and had a melting point of 96.0-100.2 C. An addi-.

tional.47.0 grams of crystals which were almost as pure were obtained by evaporating the mother liquor. The reaction may be represented by the equation:

The sample for analysis was recrystallized frompetroleum ether and had .a' melting point of 98.5-100 C. Its element analysis gave Calculated for 011111802 Found by analysis This is 1,2,3,4,tetrahydro-l, o-anisyl-l-hydroxy-naphthalene (III). Whereas no claim is made herein to this compound, it is thought to be new;

30.0 gramspf the above phenol (III) was" heated with 1.0 gram of percent palladiumcharcoal catalyst with stirring at.240-250 C. for two hours and at 250-300 C. for minutes. The catalyst had been prepared according to direction of Linstead and Thomas (J. Am. Chem.

7 800.1127 of 1940). During this treatment, about two, grams of waterv distilled outofthe mixture,.

andhydrogen was evolved. The reaction mix: ture was dissolved in benzene, filtered,{ and the benzeneimthe filtrate replaced with ethyl alcohol, On cooling, there was precipitated 25.5 grams of colorless crystalline material-of a melting. point8790' C. An additional 0.3 gram was obtainedfrom the mother liquor. Recrystalliza;

tion of the solid material from ethyl alcohol gave During this time, 200 cc. of

crystals, with a melting point of 912 -9215 'c'., which on analysis gave:

Calculated Found by analysis for CuHuO Carbon 86. 5 8'7. 2 Hydrogen 5. 9 6. 02 Oxygen (by difference) 7. 6 6. 8

tion:

Pd -C III IV 8.84 grams of the aromatic methyl ether (IV) in 200 cc. of acetic acid and 90 cc. of is-percent hydrobromic acid were refluxed 5 hours. The solution was poured on ice and extracted with benzene ether. The organic solution was washed well with water, with sodium bicarbonate, water, and saturated sodium chloride solution. After drying, the solvent was evaporated and the residue distilled to give 7.85 grams of a colorless oil. boiling at 163-170 C. (under 3 mm. pressure). This oil was made to crystallize by cooling and scratching. On recrystallizing from petroleum ether or alcohol, beautiful crystals appeared, but as soon as the solvent was removed, they lost'their OCH3 , shape and became semi-fluid. If these crystals were then scratched or allowed to stand for a long time, firm crystalline material was again obtained. V

This material is 2'-hydroxy-L-phenylnaphthae lene (V), whoseformula is, v

The melting point is 60 C. The analysis was: r

Found by Calculated analysis; fonCmHu'Q Carbon .v j 86..6 8.712 Hydrogen 5. 8f "5 .5, Oxygen (by difference) 7. 6 -731 crystals, with a melti g point of 178-190 C.

separated, Recrystallization from acetic acid a v1 Example If A'mixture of 5.0 grams of o-phenylphenol and 0.5 gram of palladium-charcoal catalyst was heated for 3 hours at 285-290 C. The mixture was extracted with petroleum ether and filtered. Unchanged o-phenylphenol was removed from the filtrate by washing with aqueous alkali. The petroleum extract was dried and chromatographed on a mixture of activated alumina and Celite. The components were selectively eluted from the column by using mixtures of petroleum ether-benzene, containing increasing quantities of benzene. The solutions were evaporated to dryness and the solids recovered. The first fraction gave a solid melting point 66-69 C., which gave no depression to the mixed melting point of diphenyl.

The later fractions gave solids with melting point 81.583 C., which gave no depression of the mixed melting point of true diphenylene oxide.

The simultaneous reactions of dehydrogenation and dehydration can be represented by the equation:

O Pd-C catalyst Diphenylene oxide Example III This example is an illustration of 'the vaporphase method.

The catalyst tube was vertical and was heated by means of a standard combustion furnace. It was similar in construction to that described in an article by one of us (Ind. Eng. Chem. Anal. Ed. 17, 673, (1945) The catalyst employed was a chromia-alumina catalyst (designated as Cr- 181 by the Harshaw Chemical Company).

During the course of two hours, 7.1 grams of molten 2-hydroxy 1 phenylnaphthalene was passed over 76 grams of the catalyst at 490 C. The partly crystalline material condensed in the receiver weighed 6.18 grams. This material was refluxed for a short time with a small volume of petroleum ether and the insoluble material filtered to give 1.4 grams with melting point 78- 91" C. Three crystallizations gave 0.47 gram of colorless crystals, melting point 96.2-96.8 C. Anal. calcd. for Ciel-I120: 87.2; H, 5.5. Found: C, 87.7; H, 5.7. The infrared absorption spectrum of the compound showed a strong band in the 2.8 micron region, indicating the presence of a hydroxy group. This compound is regarded as 2-hydroxy-2-phenylnaphthalene.

All mother liquors were combined and chromatographed on alumina-cellite. Two percolate fractions were collected; the column extruded, and arbitrarily cut into four ciractions. Fraction 4 gave 0.12 gram of material, which after two recrystallizations from ethanol, was obtained as colorless plates of melting point 209.2-209.8 C. Anal. calcd. for C1aH1OO: C, 88.1; H, 4.6. Found: C, 88.3; H, 5.1. This material was identical (melting point, mixed melting point, ultraviolet absorption spectrum) with a sample of brazan obtained from the Gezellschaft fur Teerwertung.

The reaction is believed to take place through rearrangement as follows:

Brazan is benzo b naphtho 2,3-d furan.

Other modes of applying the principle of our invention may be employed instead of those explained. Changes may be made as regards the methods or particular compounds stated provided they come within the scope of the claims.

We claim as our invention:

1. A method for the preparation of hemexanthene comprising the step of dehydrogenating a compound of the formula wherein the 2- and 8-positions in the naphthalene nucleus are unsubstituted by heating said compound in the liquid phase in the presence of a dehydrogenation catalyst.

2. The process according to claim 1 wherein the dehydrogenation catalyst comprises palladium.

3. A method for the preparation or brazan comprising the steps of dehydrogenating a compound of the formula wherein the '2- and 8-positions in the naphthalene 7 fiiee and then passing the heated vprs -over dhfilfliogfiatidn 69113211 3 817.

4. The proc'es-s according tdelaim 3 wherein the dehydrogenation. catalyst is a chro'rhiaalufififis "catalyst. l t r 5. A methbd for' the preparation of aromatic eyelid ethers Containing a: i'ahenylnaphtha'lene arqinatm nucleus eemp'rising the steps of de hydreg'natin'g a; compound of the fdrmula' wherein the 2- and 8-positions in the naphthalene nucleus are unsubstituted, by heating said com- 8 pound at least to liquefaction in the presence of a d'ehyd'rbgena'tlon catalyst. U

- V MILTONLORCHIN.

E. OSCAR WOOLFOLK.

fi EF'TE'REfieEs mm) The fq'llowing references are of record in the file of this patent:

UNITED STATES PAIENTS oTHEn ie'Efifii'tENcEs Grhin and R'ggl', J. Ghent.v sec. 70'; 1245- 0 1-247 (1948). V r 

1. A METHOD FOR THE PREPARATION OF BENZOXANTHENE COMPRISING THE STEP OF DEHYDROGENATING A COMPOUND OF THE FORMULA 